Telomere DNA length-dependent regulation of DNA replication timing at internal late replication origins

Abstract DNA replication is initiated at replication origins on chromosomes at their scheduled time during S phase of the cell cycle. Replication timing control is highly conserved among eukaryotes but the underlying mechanisms are not fully understood. Recent studies have revealed that some telomer...

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Autores principales:	Yudai Hasegawa, Mayuko Yamamoto, Junki Miyamori, Junko Kanoh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6d6e57441fd141f3b8061771df78532e
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spelling	oai:doaj.org-article:6d6e57441fd141f3b8061771df78532e2021-12-02T15:09:45ZTelomere DNA length-dependent regulation of DNA replication timing at internal late replication origins10.1038/s41598-019-46229-12045-2322https://doaj.org/article/6d6e57441fd141f3b8061771df78532e2019-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-46229-1https://doaj.org/toc/2045-2322Abstract DNA replication is initiated at replication origins on chromosomes at their scheduled time during S phase of the cell cycle. Replication timing control is highly conserved among eukaryotes but the underlying mechanisms are not fully understood. Recent studies have revealed that some telomere-binding proteins regulate replication timing at late-replicating origins throughout the genome. To investigate the molecular basis of this process, we analyzed the effects of excessive elongation of telomere DNA on replication timing by deleting telomere-associated shelterin proteins in Schizosaccharomyces pombe. We found that rap1∆ and poz1∆ cells showed abnormally accelerated replication at internal late origins but not at subtelomere regions. These defects were suppressed by removal of telomere DNA and by deletion of the telomere-binding protein Taz1. Furthermore, Sds21—a counter protein phosphatase against Dbf4-dependent kinase (DDK)—accumulated at elongated telomeres in a Taz1-dependent manner but was depleted at internal late origins, indicating that highly elongated telomeres sequester Sds21 at telomeres and perturb replication timing at internal regions. These results demonstrate that telomere DNA length is an important determinant of replication timing at internal regions of chromosomes in eukaryotes.Yudai HasegawaMayuko YamamotoJunki MiyamoriJunko KanohNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-9 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yudai Hasegawa Mayuko Yamamoto Junki Miyamori Junko Kanoh Telomere DNA length-dependent regulation of DNA replication timing at internal late replication origins
description	Abstract DNA replication is initiated at replication origins on chromosomes at their scheduled time during S phase of the cell cycle. Replication timing control is highly conserved among eukaryotes but the underlying mechanisms are not fully understood. Recent studies have revealed that some telomere-binding proteins regulate replication timing at late-replicating origins throughout the genome. To investigate the molecular basis of this process, we analyzed the effects of excessive elongation of telomere DNA on replication timing by deleting telomere-associated shelterin proteins in Schizosaccharomyces pombe. We found that rap1∆ and poz1∆ cells showed abnormally accelerated replication at internal late origins but not at subtelomere regions. These defects were suppressed by removal of telomere DNA and by deletion of the telomere-binding protein Taz1. Furthermore, Sds21—a counter protein phosphatase against Dbf4-dependent kinase (DDK)—accumulated at elongated telomeres in a Taz1-dependent manner but was depleted at internal late origins, indicating that highly elongated telomeres sequester Sds21 at telomeres and perturb replication timing at internal regions. These results demonstrate that telomere DNA length is an important determinant of replication timing at internal regions of chromosomes in eukaryotes.
format	article
author	Yudai Hasegawa Mayuko Yamamoto Junki Miyamori Junko Kanoh
author_facet	Yudai Hasegawa Mayuko Yamamoto Junki Miyamori Junko Kanoh
author_sort	Yudai Hasegawa
title	Telomere DNA length-dependent regulation of DNA replication timing at internal late replication origins
title_short	Telomere DNA length-dependent regulation of DNA replication timing at internal late replication origins
title_full	Telomere DNA length-dependent regulation of DNA replication timing at internal late replication origins
title_fullStr	Telomere DNA length-dependent regulation of DNA replication timing at internal late replication origins
title_full_unstemmed	Telomere DNA length-dependent regulation of DNA replication timing at internal late replication origins
title_sort	telomere dna length-dependent regulation of dna replication timing at internal late replication origins
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/6d6e57441fd141f3b8061771df78532e
work_keys_str_mv	AT yudaihasegawa telomerednalengthdependentregulationofdnareplicationtimingatinternallatereplicationorigins AT mayukoyamamoto telomerednalengthdependentregulationofdnareplicationtimingatinternallatereplicationorigins AT junkimiyamori telomerednalengthdependentregulationofdnareplicationtimingatinternallatereplicationorigins AT junkokanoh telomerednalengthdependentregulationofdnareplicationtimingatinternallatereplicationorigins
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Telomere DNA length-dependent regulation of DNA replication timing at internal late replication origins

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